抑酸药物COVID-19和高度可变文献的鸟瞰（再）视图
A Birds-eye (Re)View of Acid-suppression Drugs, COVID-19, and the Highly Variable Literature
摘要：
我们考虑了最近在COVID-19背景下关于抑酸药物潜在益处的信息激增，并关注了报告结果的可变性（和混乱）-至少在流行的抗酸药法莫替丁方面。这些不一致反映了在实验设计（回顾性、队列研究等）方面采用大致相似方法的独立临床研究得出的矛盾结论。和统计分析（倾向分数匹配和分层等）。这种混淆在选择治疗干预措施方面有着重大的影响：例如，法莫替丁的潜在益处是否表明其用于特定的COVID-19病例？除了这个紧迫的治疗问题，法莫替丁的冲突信息必须在其整合到本体论和知识图为基础的框架，这反过来是有用的药物再利用的努力之前得到解决。为了开始系统地构建快速积累的信息，希望澄清和调和这些差异，我们沿着三个建议的“轴”考虑矛盾的信息：（1）疾病背景轴，（2）[治疗]受益程度轴，（3）作用机制轴。我们怀疑，在过去的研究中，这些轴如何（隐含地）处理的不一致性导致了法莫替丁和COVID-19的矛盾适应症。我们还追踪了抑酸剂在COVID-19传播、严重程度和死亡率方面的信息演变，因为已经积累了许多文献报告。通过对这些研究进行概念和主题上的分组，我们确定了法莫替丁和COVID-19理解进展的三个时代。协调这些发现是临床护理标准（COVID及以后）以及基于本体论和知识图的方法的关键目标。
英文摘要：
We consider the recent surge of information on the potential benefits of acid-suppression drugs in the context of COVID-19, with an eye on the variability (and confusion) across the reported findings--at least as regards the popular antacid famotidine. The inconsistencies reflect contradictory conclusions from independent clinical-based studies that took roughly similar approaches, in terms of experimental design (retrospective, cohort-based, etc.) and statistical analyses (propensity-score matching and stratification, etc.). The confusion has significant ramifications in choosing therapeutic interventions: e.g., do potential benefits of famotidine indicate its use in a particular COVID-19 case? Beyond this pressing therapeutic issue, conflicting information on famotidine must be resolved before its integration in ontological and knowledge graph-based frameworks, which in turn are useful in drug repurposing efforts. To begin systematically structuring the rapidly accumulating information, in the hopes of clarifying and reconciling the discrepancies, we consider the contradictory information along three proposed 'axes': (1) a context-of-disease axis, (2) a degree-of-[therapeutic]-benefit axis, and (3) a mechanism-of-action axis. We suspect that incongruencies in how these axes have been (implicitly) treated in past studies has led to the contradictory indications for famotidine and COVID-19. We also trace the evolution of information on acid-suppression agents as regards the transmission, severity, and mortality of COVID-19, given the many literature reports that have accumulated. By grouping the studies conceptually and thematically, we identify three eras in the progression of our understanding of famotidine and COVID-19. Harmonizing these findings is a key goal for both clinical standards-of-care (COVID and beyond) as well as ontological and knowledge graph-based approaches.
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